PROJECT SUMMARY - OVERALL This is an application for years 46-50 funding of the Albert Einstein Cancer Center (AECC) CCSG to support basic, translational, clinical, and population based research that addresses the causes, prevention and treatment of cancer. In September 2015, ownership of the Albert Einstein College of Medicine transferred from Yeshiva University to Montefiore Medicine. The AECC and its clinical partner, the Montefiore Health System, now both under the Montefiore Medicine umbrella, are the major providers of cancer care and prevention programs to the largely minority, and socioeconomically challenged, 1.4M residents of the Bronx. There are five established AECC programs: The Tumor Microenvironment and Metastasis Program which brings together advanced in in vivo imaging technologies and innovative mouse models focused on breast cancer, with recent extension to other neoplasms, and translation into diagnostic, correlative and therapeutic studies in humans. The Stem Cells, Differentiation and Cancer Program encompasses three interrelated themes - stem cell biology, hematological malignancies, and a component focused on basic investigations on epigenetics/ transcription mechanisms and chromatin biology. The Experimental Therapeutics Program is the home for the conduct of all clinical therapeutic trials, and the translation of basic discoveries into investigator-initiated clinical initiatives, at AECC. The program is also the focal point for the development of small molecule inhibitors, and novel immuno-therapeutics, for the treatment of cancer. The Cancer Epidemiology, Prevention and Control Program, evolved from the prior Cancer Epidemiology Program, reflecting the expanded scope of population- based research that encompasses infectious, metabolic, endocrine, obesity-related and genetic/epigenetic causes of cancer and their prevention and control. The Biology of Colon Cancer Program focuses on the convergence of dietary and genetic factors, along with the role of aging, in the pathogenesis of colorectal cancer using mouse models of human cancer now encompassing studies on intestinal stem cells, the microbiome and the villus niche with the objective of translating preclinical findings into prevention strategies. There is research directed to the Bronx catchment area in all five AECC research programs, now brought together with the inauguration of the Community Outreach and Engagement component and units within the Montefiore organization, that provide well-established, effective surveillance, education and outreach capabilities. This, along with the strong clinical electronic informatics at Montefiore and AECC, provide the tools and support that expand the Center's research and implementation capabilities directed to the Bronx population. There are twelve shared resources, including the recent addition of a Chemical Synthesis Shared Resource, that support the spectrum of AECC research activities. There are currently 144 AECC members representing 23 departments with a cancer relevant direct cost funding base of $21M NCI, $18M other NIH, $4M in our peer-review grants, totaling $41M in total peer-reviewed grants.